The proposed studies will extend our research to develop a defined vaccine against schistosomiasis. The experiments are based on our demonstration that multiple antigen synthetic peptide (MAPs) vaccines for the candidate antigens sTPI and Sm23, and a DNA vaccine for Sm23 are highly efficacious against parasite challenge in mice. The proposed studies will future examine the mechanism of sTPI and Sm23 MAP induced immunity by testing efficacy of T cell only sTPI MAP and a new Sm23 Map. In regards to DNA vaccines, we will test efficacy of two DNA vaccines based on sTPI coding regions, one of which is the coding region for the T and B cell epitopes found in MAP4; then test a dual antigen DNA vaccine containing sTPI T-B epitopes incorporated within the Sm23 coding region. One goal of the proposal is to determine if combinations of antigens enhance efficacy or allow for successful immunization even when the response to one of the antigens is genetically restricted. The adjuvant potential of IL-12 and B7 plasmid DNAs in concert with Sm23 and sTPI vaccines will be measured. To further determine optimal parameters for DNA vaccines, we will compare vaccine efficacy after immunization via intramuscular, microseeding and ~gene gun~ routes. To determine if CD4plus Th-type bias of patients will have an effect on vaccine efficacy, we will test vaccine efficacy in mice which have been made. Th2-biased, due to prior or concurrent infection with S. Mansoni or intestinal nematode infections. Prior to moving to human trails, we will perform vaccine trials in baboons with optimized Sm23 and sTPI vaccines. Lastly, because Sm23 and sTPI from S. mansoni are very similar to the S. japonicum homologues, we ask if Sm23 and sTPI based vaccines will also protect against S. japonicum infection. The specific aims of this proposal are: 1) Can the efficacy of Sm23 and sTPI peptide vaccines be enhanced/optimized by immunizing with new Map constructs and/or combinations of MAPs?: 2) Will sTPI or Sm23-TPI DNA vaccines induce/enhance protective immune responses in mice?: 3) Is DNA vaccine efficacy altered as a function of vaccination route or use of cytokine/co-stimulatory molecules as adjuvants?: 4) Does host immune bias (CD4plus Th- type) play a role in efficacy of Sm23 or sTPI peptide and DNA vaccines?: 5) Will Sm23 and sTPI peptide and DNA vaccines be immunogenic and /or protective in baboons?: 6) Can vaccines based on Sm23 and sTPI protect against S. japonicum infection in mice and piglets?